title: Clinical review: The role of the parent compound vitamin D with respect to metabolism and function: Why clinical dose intervals can affect clinical outcomes.
abstract: BACKGROUND
  There is no doubt that vitamin D must be activated to the hormonal form 1,25-dihydroxyvitamin D to achieve full biological activity or that many tissues participate in this activation process-be it endocrine or autocrine. We believe that not only is 25-hydroxyvitamin D important to tissue delivery for this activation process, but also that intact vitamin D has a pivotal role in this process.
  
  
  OBJECTIVE
  In this review, evidence on the vitamin D endocrine/autocrine system is presented and discussed in relation to vitamin D-binding protein affinity, circulating half-lives, and enzymatic transformations of vitamin D metabolites, and how these affect biological action in any given tissue.
  
  
  CONCLUSIONS
  Circulating vitamin D, the parent compound, likely plays an important physiological role with respect to the vitamin D endocrine/autocrine system, as a substrate in many tissues, not originally thought to be important. Based on emerging data from the laboratory, clinical trials, and data on circulating 25-hydroxyvitamin D amassed during many decades, it is likely that for the optimal functioning of these systems, significant vitamin D should be available on a daily basis to ensure stable circulating concentrations, implying that variation in vitamin D dosing schedules could have profound effects on the outcomes of clinical trials because of the short circulating half-life of intact vitamin D.
authors.affiliation: PhD, Medical University of South Carolina, 173 Ashley Avenue, MSC 514, Charleston, SC 29425. hollisb@musc.edu.
authors.forename: Bruce W
authors.initials: BW
authors.lastname: Hollis
authors.forename: Carol L
authors.initials: CL
authors.lastname: Wagner
mesh_terms: D015652:25-Hydroxyvitamin D 2 / Q000097:blood / Q000378:metabolism; D000818:Animals; D019898:Autocrine Communication; D002112:Calcifediol / Q000097:blood / Q000378:metabolism; D002117:Calcitriol / Q000097:blood / Q000378:metabolism; D019587:Dietary Supplements; D004703:Endocrine System / Q000378:metabolism*; D004700:Endocrine System Diseases / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control; D004872:Ergocalciferols / Q000097:blood / Q000378:metabolism; D006801:Humans; D014807:Vitamin D / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism* / Q000627:therapeutic use; D014808:Vitamin D Deficiency / Q000178:diet therapy / Q000378:metabolism / Q000503:physiopathology
chemical_list: D004872:Ergocalciferols; D014807:Vitamin D; D015652:25-Hydroxyvitamin D 2; C003564:1,25-dihydroxyergocalciferol; D002117:Calcitriol; D002112:Calcifediol